PMID- 1497091 OWN - NLM STAT- MEDLINE DCOM- 19920910 LR - 20220316 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 141 IP - 2 DP - 1992 Aug TI - Cytokine-induced neutrophil-derived interleukin-8. PG - 397-407 AB - During acute inflammation, the first line of cellular response for host defense is the neutrophil. In addition to the historic role of the neutrophil as a phagocyte, recent studies have identified this cell as an important source of a number of cytokines. In this study, we provide evidence that the neutrophil is a significant source of interleukin-8 (IL-8). Neutrophils freshly isolated from whole blood were not found to constitutively express IL-8 mRNA. In contrast, when these leukocytes were cultured on plastic they were activated, leading to the significant expression of de novo steady-state levels of IL-8 mRNA. In addition, when neutrophils were treated with cycloheximide, there was evidence for "superinduction" of steady-state levels of IL-8 mRNA and inhibition of antigenic IL-8 production. Neutrophils were subsequently stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha, or interleukin-1-beta and were found to express IL-8 mRNA and antigen in both a time- and dose-dependent manner. Furthermore, neutrophils stimulated with traditional chemotactic/activating factors, such as the split product of the fifth component of complement (C5a), formylmethionyleucylphenylalanine (fMLP), and leukotriene B4 (LTB4) in a dose-dependent manner did not produce significant antigenic IL-8, as compared with unstimulated controls. In contrast, when neutrophils were exposed to either of these neutrophil agonists in the presence of LPS, the production of antigenic IL-8 was significantly elevated, as compared with either of the stimuli alone, suggesting a synergistic response. These data would suggest that the neutrophil can no longer be viewed as only a phagocyte or warehouse for proteolytic enzymes, but is a pivotal effector cell that is able to respond to mediators in its environment and generate cytokines. This latter neutrophil response may be important for either the elicitation of additional neutrophils or to orchestrate the conventional immune response at sites of inflammation. FAU - Strieter, R M AU - Strieter RM AD - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360. FAU - Kasahara, K AU - Kasahara K FAU - Allen, R M AU - Allen RM FAU - Standiford, T J AU - Standiford TJ FAU - Rolfe, M W AU - Rolfe MW FAU - Becker, F S AU - Becker FS FAU - Chensue, S W AU - Chensue SW FAU - Kunkel, S L AU - Kunkel SL LA - eng GR - HL 02401/HL/NHLBI NIH HHS/United States GR - HL 31693/HL/NHLBI NIH HHS/United States GR - IP50 HL 46487/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antigens) RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Interleukin-8) RN - 0 (Lipopolysaccharides) RN - 0 (Plastics) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Antigens/analysis MH - Cell Adhesion MH - Cytokines/*pharmacology MH - Dose-Response Relationship, Drug MH - Drug Synergism MH - Humans MH - Immunohistochemistry MH - Interleukin-1/pharmacology MH - Interleukin-8/genetics/immunology/*metabolism MH - Lipopolysaccharides MH - Neutrophils/*metabolism/physiology MH - Plastics MH - RNA, Messenger/metabolism MH - Time Factors MH - Tumor Necrosis Factor-alpha/pharmacology PMC - PMC1886610 EDAT- 1992/08/01 00:00 MHDA- 1992/08/01 00:01 PMCR- 1993/02/01 CRDT- 1992/08/01 00:00 PHST- 1992/08/01 00:00 [pubmed] PHST- 1992/08/01 00:01 [medline] PHST- 1992/08/01 00:00 [entrez] PHST- 1993/02/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1992 Aug;141(2):397-407.